Shapiro R S, McClain K, Frizzera G, Gajl-Peczalska K J, Kersey J H, Blazar B R, Arthur D C, Patton D F, Greenberg J S, Burke B
Department of Pediatrics, University of Minnesota Hospital and Clinic, Minneapolis 55455.
Blood. 1988 May;71(5):1234-43.
B cell lymphoproliferative disorders (BLPD) developed in eight patients following bone marrow transplantation (BMT) for leukemia (five patients) or immunodeficiency (three patients). Recipients of T depleted marrow from a mismatched donor were at particularly high risk of this complication. Six of 25 (24%) recipients of mismatched T depleted bone marrow developed BLPD. In contrast, none of 47 matched T depleted transplants, one of ten (10%) who received non-depleted marrow from an unrelated donor, and only one of 424 matched non-depleted transplants were associated with BLPD. Epstein-Barr virus (EBV) specific serology and DNA hybridization studies demonstrating five to 50 copies of EBV genome/cell in involved tissues implicate this virus as an associated etiologic agent. Restriction fragment length polymorphism (RFLP) and cytogenetic analysis of involved tissue demonstrated donor origin (five of seven) or host origin (two of seven). Histologic appearance was similar to EBV-induced polymorphic B cell proliferations described following solid organ transplantation, or which occur de novo in primary immunodeficiency. Six of seven patients with adequate tissue available for study were found to have monoclonal proliferations by: in situ immunofluorescence (six of seven), and/or immunoglobulin gene rearrangement, (four of six). Cytogenetic analysis of involved tissues from four patients showed a normal karyotype, whereas two had multiple clonal chromosomal abnormalities. Seven patients died despite aggressive attempts at therapy with combinations of antiviral, immunologic, and chemotherapeutic agents.
8例患者在接受白血病（5例）或免疫缺陷（3例）的骨髓移植（BMT）后发生了B细胞淋巴增殖性疾病（BLPD）。接受来自不匹配供体的T细胞去除骨髓的受者发生这种并发症的风险特别高。25例接受不匹配T细胞去除骨髓的受者中有6例（24%）发生了BLPD。相比之下，47例匹配的T细胞去除移植受者中无一例发生BLPD，10例接受无关供体非去除骨髓的受者中有1例（10%）发生BLPD，424例匹配的非去除移植受者中只有1例发生BLPD。爱泼斯坦-巴尔病毒（EBV）特异性血清学和DNA杂交研究表明，受累组织中EBV基因组/细胞有5至50个拷贝，提示该病毒是相关的病原体。对受累组织的限制性片段长度多态性（RFLP）和细胞遗传学分析显示起源于供体（7例中的5例）或宿主（7例中的2例）。组织学表现类似于实体器官移植后描述的EBV诱导的多形性B细胞增殖，或原发性免疫缺陷中发生的原发性EBV诱导的多形性B细胞增殖。7例有足够组织可供研究的患者中，有6例通过以下方法发现有单克隆增殖：原位免疫荧光（7例中的6例）和/或免疫球蛋白基因重排（6例中的4例）。对4例患者受累组织的细胞遗传学分析显示核型正常，而2例有多个克隆性染色体异常。尽管积极尝试联合使用抗病毒、免疫和化疗药物进行治疗，7例患者仍死亡。
